OP0053 EFFICACY AND SAFETY OF BARICITINIB IN PATIENTS WITH ACTIVE LUPUS NEPHRITIS: A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED PHASE 3 TRIAL
Authors: M. Hassanien, A. Moshrif, H. Hetta
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Baricitinib a selective Janus kinase (JAK) inhibitors 1&amp;2 have been recognized as a potential therapeutic option in systemic lupus (SLE), also known Baricitinib, a JAK inhibitor, has demonstrated efficacy and safety in the treatment of dermatitis and arthritis 1; however, no JAK inhibitor studies have been conducted in lupus nephritis (LN) to dat.e. <h3>Objectives</h3> To assess the efficacy and safety of Baricitinib in patients (pts) with active LN. <h3>Methods</h3> The study is a randomized, double-blind, active competitor (cyclophosphamide)-controlled, phase 3 trial registered on clinicaltrials.com (NCT05432531), enrolled adults ≥18 years with a clinical diagnosis of LN (who also fulfilled classification criteria for LN grade III &amp; IV), who had objective signs of active nephritis consistent with persistent proteinuria&gt;0.5 g/day and/or cellular casts at screening, and who had SLEDAI-2K &gt; 4 and patient assessment of anti-ds DNA and C3 serum levels at study entry. Pts were randomized 1:1 to receive Group 1: oral Baricitinib 4mg once daily and PBO saline infusion monthly, Group 2: oral PBO tablet and cyclophosphamide (0.7mg/m2) infusion monthly during a 6-months double-blind treatment period. The primary endpoint was proteinuria, response at week 12 and 24. Multiplicity-controlled secondary endpoints assessed at week 12 &amp;24 included C3, anti-ds-DNA and SLEDAI-2K, and their changes from baseline, Treatment adverse events was recorded. <h3>Results</h3> Of 65 pts randomized at baseline, 60 enrolled in the study (Baricitinib 4mg, n=30; cyclophosphamide, n=30) and 100% received study drug through week 24. Baseline demographic and disease characteristics were balanced across treatment groups and consistent with an active LN population, all were females, 58% LN grade III; mean age 32.4 years; mean SLEDAI-2K 6.9; mean C3 12.1mg/L). A significantly reduction in proteinuria response rate at week 12 was achieved in group 1 vs group 2 (70% vs 43%; P&lt;0.0001). Statistical significance was also achieved in the first 12 of the 24 w multiplicity-controlled secondary endpoints (C3 and SLEDAI-2k) at week 12 in group 1 compared with group 2 (P&lt;0.01). The proportion of pts who experienced adverse events was similar between treatment groups (group 1, 48%; group 2, 46%). Serious adverse events leading to discontinuation were reported in 2 (6.6%) pts treated with Baricitinib and 1 (3.3%) pts treated with cyclophosphamide, respectively (serious infection or herpes zoster), major adverse cardiovascular events, venous thromboembolic events, were not reported in the study. <h3>Conclusion</h3> Baricitinib 4mg once daily demonstrated significantly good improvements in disease activity, proteinuria, C3, anti-ds-DNA, than cyclophosphamide after 12 &amp;24 weeks of treatment in pts with active LN. The safety profile of Baricitinib 4mg was consistent with what has been observed with other inflammatory musculoskeletal diseases, and no new risks were identified. These results support the potential use of Baricitinib 4mg in pts with active LN. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.